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Phase I clinical trial of lenalidomide in combination with 5-fluorouracil, leucovorin, and oxaliplatin in patients with advanced cancer

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Abstract

Purpose

Lenalidomide has synergistic anticancer effects when used with chemotherapy. We conducted a phase I study of lenalidomide in combination with FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) in patients with advanced cancer.

Methods

A “3 + 3” study design was used. Lenalidomide was given orally on days 1–14, oxaliplatin and leucovorin were given intravenously on day 1, and 5-fluorouracil was given as a continuous infusion on days 1–2. The dose escalation phase of the study was followed by an expansion phase. We assessed the maximum tolerated dose, dose-limiting toxicities, and response.

Results

Thirty-eight patients were treated [median age 53 years (range 31–76); male/female 20:18]. The most common diagnosis was colorectal cancer (CRC) (n = 30, 79 %). Overall, 132 cycles (median 2/patient) were administered. No dose-limiting toxicities were observed. The maximum tested dose (dose level 4) was used in the expansion phase. Grade 3/4 treatment-related toxicities (all reversible) were seen in 14 (37 %) patients and included neutropenia (n = 11), thrombocytopenia (n = 2), and fatigue (n = 2). There were no thrombotic events. Response was evaluable in 32 patients: 19 (59 %) had stable disease (SD), including SD ≥6 months in 4 (13 %) patients. Tumor types with SD ≥6 months were CRC (n = 2; progression-free survival [PFS] 11.3 and 7.1 months, respectively), gastric (n = 1; PFS 8.5 months), and pancreatic (n = 1; PFS 6.4 months) cancer. The median PFS and overall survival durations were 2.2 months (range <1.3–23) and 5.5 months (range <1.6–23), respectively.

Conclusions

Lenalidomide in combination with FOLFOX was well tolerated. Four patients had prolonged stable disease. This combination merits further investigation for selected patient populations.

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Acknowledgments

Funding

This work was supported by the National Cancer Institute at the National Institutes of Health under Grant P30CA016672. This research was supported by a research Grant from Celgene protocol, 2010-0108, to Dr. Tsimberidou.

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Authors and Affiliations

  1. Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Rabih Said, Yang Ye, David S. Hong, Aung Naing, Siqing Fu, Jennifer J. Wheler, Sarina Piha-Paul & Apostolia-Maria Tsimberidou

  2. Department of Internal Medicine, The University of Texas Health Science Center, Houston, TX, USA

    Rabih Said

  3. Sarah Cannon Research Institute, Denver, CO, USA

    Gerald Falchook

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  1. Rabih Said
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  2. Yang Ye
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Correspondence to Apostolia-Maria Tsimberidou.

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Said, R., Ye, Y., Hong, D.S. et al. Phase I clinical trial of lenalidomide in combination with 5-fluorouracil, leucovorin, and oxaliplatin in patients with advanced cancer. Cancer Chemother Pharmacol 77, 575–581 (2016). https://doi.org/10.1007/s00280-015-2952-z

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